The X chromosome of Drosophila melagnogaster is capable of at least four different levels of transcriptional activity: the male level which is twice that achieved in females (dosage compensation), an intermediate level in intersexes, and a lower level in metafemales. This system will be used as tool with which to study the regulation of gene expression in a complex eukaryote. Two major approaches are proposed: an extensive attempt to characterize some major features of the functional organization of the genetic material, and a preliminary study of putative regulatory molecules. Genetic means will be employed to search for and characterize autosomal regulators of X-linked gene expression. Mutant screens and fine structure genetic analysis will be employed to uncover and order regulatory sites linked to structural genes on the X chromosome. Biochemical methods will be used to study the molecular mechanisms involved in gene regulation. In particular, the use of the system to study the regulatory role of nuclear acidic proteins will be investigated.